June 16, 2011 -- Psilocybin, a powerful psychoactive substance derived from magic mushrooms, can safely be used in a controlled setting to help people have positive and often life-altering experiences, a new study shows.

The study is part of a renaissance of research into the benefits of hallucinogenic drugs that were first popularized, and villainized, in the counterculture movements of 1960s.

Ongoing clinical trials are testing agents like LSD, psilocybin, and mescaline to treat alcoholism and other addictions and to ease anxiety and depression in people who are dying of cancer.

Though early results from small studies have been promising, little is known about how best use these powerful mind-bending medications.

Hallucinogens as Therapeutic Tools

The new study, from researchers at Johns Hopkins University School of Medicine in Baltimore, tested different dosing regimens of psilocybin in 18 healthy adult volunteers.

"Previously, we looked at a single high dose of and showed that it occasioned these mystical-type experiences that had profoundly meaningful and spiritually significant effects," says study researcher Roland Griffiths, PhD, professor of psychiatry and behavioral sciences and neuroscience at Hopkins.

After trying psilocybin just one time, many of the volunteers in that 2006 study reported having profound spiritual and mystical experiences that made them more open and honest, less judgmental, and closer to family and friends, and some rated it as the most personally meaningful experience of their lives.

But about one-third of those volunteers also experienced transient periods of overwhelming fear and anxiety. They felt afraid that they were trapped, for example, or that they were going to go insane. Most of the time, those feelings passed during the session, but in a few cases, they went on for hours.

"That's known to be one of the risks of recreational use of these compounds: People can have panic reactions, fearful reactions, and the danger is that they're going to engage in dangerous behaviors that then put themselves or others at risk," Griffiths says.

In the new study, Griffiths and his team found that when the dose of psilocybin was reduced slightly, most people still had the transformative mystical experience, with far less fear and anxiety.

"The optimal dose appears to be lower than what we were using," he says. "You can back the dose down and pretty dramatically, like fivefold, decrease the rates of these fearful anxiety responses while only marginally decreasing the mystical-type experiences."

Nearly 75% of the study volunteers reported having positive, highly beneficial experiences on the two highest psilocybin doses used in the study. Almost half rated taking the drug in a supportive, therapeutic setting as the single most meaningful experience of their lives.

The study is published in Neuropsychopharmacology.

Recreational Use Can Be Dangerous

This is not to suggest, experts say, that people should use psilocybin or hallucinogenic mushrooms recreationally.

"This is still very much an investigational drug," says Charles S. Grob, professor of psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles.

"This study should not at all be suggested to individuals to be trying compounds like this on their own. We're exploring whether or not there could be a therapeutic application when these drugs are taken within a treatment setting," says Grob, who studies psilocybin but was not involved in the current research.

There are important safeguards when psilocybin is tested in clinical settings that are not in place when the drugs are used recreationally.

For one thing, doctors are testing standardized doses of psilocybin that are given in capsules.

"No one really knows, if they're taking mushrooms, what the content of the psilocybin is," Griffiths says. "Within mushrooms, the content of psilocybin can vary tenfold."

And very rarely, he says, people have become so fearful or panicked that they have reportedly jumped out of windows or run into traffic. Also, for certain individuals with a genetic predisposition, hallucinogens may tip their brains into psychosis.

"For people who have some vulnerability to psychotic disorder, this might push them over the edge into schizophrenia," he says.

Tracking the Effects of Psilocybin

For the study, Griffiths and his team recruited 18 physically and mentally healthy adults.

Each study participant was given four doses of psilocybin, with a month between each dose. Doses were based on body size and were 5 mg, 10 mg, 20 mg, or 30 mg for every 154 pounds of body weight. A placebo dose was also given.

Participants were randomly assigned to receive either gradually increasing doses or gradually decreasing doses, to test a hypothesis that it might be more effective to start with a high initial dose.

Neither the study participants nor researchers knew what group the participants were in or what dose of the drug they were going to get when they showed up for their sessions.

Sessions were conducted in a lab furnished to look like a living room. Study volunteers were encouraged to wear an eye mask to control visual stimulation and to lie down on a couch. They listened to music through headphones. They were encouraged to inwardly focus their attention. Two trained monitors stayed in the room throughout the test session, which lasted about eight hours.

About 40% of study participants, or seven out of 18, reported feeling extreme anxiety and fear while they were on the two highest doses of the drug. Six of the seven, however, experienced the fear while on the highest dose of the drug. Only one person reported negative fear effects on the 20 mg dose.

Examples of the delusions experienced by study participants included the belief that a child or loved one had died while the session was ongoing or that that the monitors were being cruel or manipulative.

Some experts say those negative feelings shouldn't necessarily be avoided, especially if people are trying to work through addictions or end-of-life issues.

"When you work with people that have emotional issues, they are going to have difficult experiences," says Rick Doblin, PhD, director of the Multidisciplinary Association for Psychedelic Studies in Santa Cruz, Calf. "Those are emotions that we anticipate, and to a certain degree, people need to work through them."

Indeed, many people who went through so-called "bad trips" also reported that the feelings were eventually replaced by more positive thoughts during the same session, and none reported that the fear or anxiety they experienced caused any long-term harm.

In contrast, nearly three out of four people on the highest psilocybin doses rated their experiences as mystical, transformative, and highly beneficial.

"The core of the mystical experience is a sense of the interconnectedness of all people and things," says Griffiths. "That's accompanied by a sense of sacredness, a sense of the experience being more real and more true than everyday waking consciousness."

Many reported that the drug facilitated lasting positive changes leading to better marriages, friendships, and family relationships. Many also reported taking better care of themselves and enjoying life more.

"If you really get this sense at the core of your soul, that we're connected to a greater whole, and I think we all know this at some level ... there's something about that that's very benevolent and uplifting and positive," Griffiths says.

Notably, the positive changes reported by participants have lasted more than 14 months after their last sessions.

The study shows, says Grob, "You don't need to induce a frightening experience to facilitate a very positive therapeutic outcome."